Iron is an essential element required for microbial growth. In the environment and in body tissues and fluids, this metal remains in a bound or precipitated form and is therefore unavailable for use by microbial cells. Many microorganisms, have been shown to produce small molecular weight compounds called siderophores that may selectively chelate iron and thereby facilitate its use by the organism. By their ability to acquire iron, these specific chelating compounds might serve as virulence factors in that they enable microbial species to infect tissues by making available the essential metal, iron. Experiments will carried out to determine the role of a siderophore produced by Histoplasma capsulatum in the establishment of experimental disease. The siderophore will be purified by extraction and chemically characterized by determining its amino acid composition, and spectra by visible, infrared and mass spectroscopy. The roles of Histoplasma siderophore and iron in histoplasmosis will be studied. Growth will be determined by plate count of yeast phase cells. An attempt will be made to correlate virulence (LD50) with ability of Histoplasma to produce siderophore in culture. The effect of siderophore and iron on experimental histoplasmosis in mice will be determined by quantitative culture of infected organs and should give an indication of the relative importance of the two in establishment of disease.